Targeting NOX2 via p47/phox-p22/phox Inhibition with Novel Triproline Mimetics.

ABSTRACT: On the basis of the knowledge that the proline-rich hot spot PPPRPP region of P(151)PSNPPPRPP(160), an oligopeptide derived from the cytosolic portion of p22^phox (p22), binds to the single functional bis-SH3 domain of the regulatory protein p47^phox (p47), we designed a mimetic of the tripeptide PPP based on NMR and X-ray crystallographic data for the p22(151-161) peptide PPSNPPPRPPA with a peptide construct. Incorporation of the synthetic pseudo-triproline mimetic Pro-Pro-Cyp in a molecule derived from molecular modeling studies led to only a 7-fold diminution in activity in a surface plasmon resonance assay relative to the same molecule containing the natural Pro-Pro-Pro tripeptide. The alternative sequence corresponding to a Pro-Cyp-Pro insertio

SUBMITTER: Garsi JB 

PROVIDER: S-EPMC9190036 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature